Haematological Changes in Systemic Disease Flashcards
What are the main 4 types of haematological disorders?
Haemostasis and thrombophilia
Haematological oncology
Red cell disorders
Immune haematology
What broadly happens in haemostasis and thrombophilia?
Altered function of solube=le proteins e.g. FVIII deficiency, Protein C deficiency
Platelet function & interaction with endothelial surfaces
What are the main causes of haematological oncology?
Primary abnormalities of white cell production and differentiation
What are the common red cell disorders?
Inherited (sickle cell, thalassaemia) acquired
What are the main immune haematology conditions?
Auto immune cytopenias
What is often the fundamental problem in haematological conditions?
Excesses or deficiencies
What is the result of a deficiency of Factor VIII?
Haemophilia A –> bleeding
What is the result of a deficiency of Protein C?
Pro-thrombotic
What is the name of an excess of erythrocytes?
Polycythaemia
What is the name of a deficiency of erythrocytes?
Anaemia
What could be the cause of excess of granulocytes?
Leukaemia (CML)
Reactive eosinophilia
What could be the cause of excess lymphocytes?
Leukaemia (CLL)
What could be the cause of lymphocyte deficiency?
HIV –> lymphopenia
What is the name for a raised platelet count?
Essential thrombocythemia
What is the name of platelet deficiency precipitated by infection?
Immune thrombocytopenic purpura (ITP)
Define primary haematological disorders
Primary disorders arise from DNA mutations and are diseases of the bone marrow or blood
Define secondary haematological disorders
Changes in haematological parameters secondary to a non-haematological disorder
What condition is a FIX deficiency?
Haemophilia B
Give examples of primary erythrocyte disorders
Deficiency - beta globin chain production –> beta Thalassaemia
Excess –> VHL gene –> Chuvash polycythaemia
Give an example of a primary acquired erythrocyte disorder
Excess –> JAK2 V617F –> Polycythaemia vera
Given an example of a primary acquired myeloid/granulocyte disorder
BCR-ABL1 –> Chronic myeloid leukaemia
Give an example of a secondary disorder causing excess erythrocytes
Cyanotic heart disease –> hypoxia –> excess erythrocytes
Give an example of a secondary disorder leading to decreased erythrocytes
Immune haemolysis –> anti-RBC antibodies –> deficiency
Given an example of a secondary disorder that can lead to FVIII excess
Inflammatory response –> FVIII excess
Give an example of a secondary disorder that leads to FVIII deficiency
anti-FVIII auto-antibodies in acquired haemophilia A –> FVIII deficiency
Fe deficiency is
Bleeding until proven otherwise
If Fe is found and there is an underlying malignancy, what will the blood tests show?
Fe deficiency
Microcytoic hypochronic anaemia
Reduced ferritin, transferrin saturation
Raised total iron binding capacity (TIBC)
What may cause occult blood loss?
GI cancers - gastric, colorectal
Urinary tract cancers - renal cell carcinoma, bladder cancer
What is a leuco-erythroblastic anaemia?
Variable degree of anaemia
What are the blood film features in leuco-erythroblastic anaemia?
Teardrop RBCs (+aniso and poikilocytosis)
Nucleated RBCs
Immature myeloid cells
Normal peripheral blood film features
No nucleated RBCs
Mature cells
Leucoerythroblastic film
Tear drop poikilocytes
Nucleated RBCs
Myelocyte
What must have happened for a leucoerythroblastic film?
Bone marrow infiltration
What are the causes of bone marrow infiltration?
Sever infection - miliary TB, severe fungal infection
Myelofibrosis - massive splenomegaly, dry tap on BM aspirate
Malignant - Haemopoietic (leukaemic/lymphoma/myeloma), non-haemopoietic (metastatis breast/bronchus/prostate)
What are the common laboratory features of all haemolytic anaemias?
Anaemia (though may be compensated) Reticulocytosis Unconjugated bilirubin raised (pre-hapatic) LDH raised Haptoglobins reduced
What are the groups of haemolytic anaemias?
Inherited (primary) - defects of the red cell/germline DNA mutation
Acquired (secondary) - defects of the environment in which the red cell finds itself i.e. systemic disease
Give examples of primary haemolytic anaemias
Membrane e.g. Hereditary Spherocytosis
Cytoplasm/enzymes e.g. G6PD deficiency
Haemoglobin e.g. Sickle cell disease (structural) Thalassaemia (quantitative)
What are the types of acquired (secondary) haemolytic anaemias?
Non immune (DAT -ve) Immune mediated (DAT +ve, direct antiglobulin test i.e. Coombs test)
What are the key features of immune haemolytic anaemia?
Spherocytes
DAT +ve (Coombs test)
What systemic diseases are associated with immune haemolytic anaemia?
Malignancy e.g. Lymphoma, CLL
Auto immune e.g. SLE
Infection e.g. mycoplasma
Idiopathic
What are some non-immune causes of acquired haemolytic anaemia?
Infection e.g. malaria
Micro-angiopathic Haemolytic anaeia (MAHA) - underlying adenocarcinoma, haemolytic uraemic syndrome
Micro-angiopathic haemolytic anaemia blood film
RBC fragments
Thrombocytopenia
Why does MAHA cause RBC fragments?
Platelet activation –> fibrin deposition and degradation –> red cell fragmentation (microangiopathy) –> bleeding (low platelets and coag factor deficiency)
What types of white blood cells are found in bone marrow?
Blasts (myeloid & lymphoid)
Promyelocytes
Myelocytes
What white blood cells are found in peripheral blood?
Phagocytes: granulocytes - neutrophils, eosinophil, basophils. monocytes
Immunocytes: T lymphocytes, B lymphocytes
What are the immediate concerns if immature cells are seen in the peripheral blood?
Leukaemia or metastatic cancer invading bone marrow
What can cause neutrophilia (raised neutrophil count)?
Pyogenic infection Corticosteroids Underlying neoplasia Tissue inflammation e.g. colitis, pancreatitis Myeloproliferative/leukaemic disorders
How would you identify a reactive/infection neutrophilia?
Neutrophilia + toxic granulation no immature cells
How would you identify a malignant neutrophilia?
Neutrophilia plus basophilia & immature cells myelocytes. Suggest a myeloproliferative (CML)
Neutrophenia plus myeloblasts suggests acute leukaemia (AML)
Reactive neutrophilia blood film
Only mature cells, toxic granules in neutrophils
CML blood film
Neutrophilia
Immature cells (myelocytes)
Basophils
Give some causes of reactive eosinophilia
Parasitic infection
Allergic disease e.g. asthma, rheumatoid, polyarteritis, pulmonary eosinophilia
Underlying neoplasms esp. Hodgkin’s, T-cell NHL
Drugs (reaction erythema multiforme)
What could be a primary cause of eosinophilia?
Chronic eosinophilic leukaemia
What can cause monocytosis?
TB, brucella, typhoid
Viral: CMV, varicella zoster
Sarcoidosis
Chronic myelomonocytic leukaemia (MDS)
What can cause lymphocytosis (raised lymphocytes)?
EBC, CMV, toxoplasma
Infectious hepatitis, rubella, herpes infections
Autoimmune disorders
Sarcoidosis
What can cause lymphopenia?
Infection e.g. HIV
Auto immune disorders
Inherited immune deficiency syndromes
Drugs (chemotherapy)
What is the cause if there are mature lymphocytes in the blood with no atypical cells?
Reactive/infectious cause
What is the cause if there are mature lymphocytes in the blood in addition to small lymphocytes and smear cells?
CLL
NHL
If there are lymphoblasts present in the peripheral blood what is the cause?
Acute lymphoblastic leukaemia
Chronic lymphocytic leukaemia blood film
Mature lymphoid cells
Acute lymphobastic leukaemia blood film
Immature lymphoid cells
What is the light chain ratio/clonality in reactive lymphocytosis?
Polyclonal
Kappa & Lambda 60:40
What is the light chain ratio/clonality in malignant lymphocytosis?
Kappa only or lambda only
99:1 malignant
